Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas

Serena Pellegatta, Pietro Luigi Poliani, Daniela Corno, Francesca Menghi, Francesco Ghielmetti, Bianca Suarez-Merino, Valentina Caldera, Sara Nava, Maria Ravanini, Fabio Facchetti, Maria Grazia Bruzzone, Gaetano Finocchiaro

Research output: Contribution to journalArticle

Abstract

Cancer stem-like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P <0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P <0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination.

Original languageEnglish
Pages (from-to)10247-10252
Number of pages6
JournalCancer Research
Volume66
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

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Neoplastic Stem Cells
Glioma
Dendritic Cells
Neoplasms
Immunotherapy
Vaccination
Fibroblast Growth Factor 2
Glioblastoma
Survival Analysis
Oligonucleotide Array Sequence Analysis
Epidermal Growth Factor
Neuroglia
Real-Time Polymerase Chain Reaction
Histology
Stem Cells
Bone Marrow
Immunohistochemistry
Magnetic Resonance Imaging
Clinical Trials
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. / Pellegatta, Serena; Poliani, Pietro Luigi; Corno, Daniela; Menghi, Francesca; Ghielmetti, Francesco; Suarez-Merino, Bianca; Caldera, Valentina; Nava, Sara; Ravanini, Maria; Facchetti, Fabio; Bruzzone, Maria Grazia; Finocchiaro, Gaetano.

In: Cancer Research, Vol. 66, No. 21, 01.11.2006, p. 10247-10252.

Research output: Contribution to journalArticle

Pellegatta, Serena ; Poliani, Pietro Luigi ; Corno, Daniela ; Menghi, Francesca ; Ghielmetti, Francesco ; Suarez-Merino, Bianca ; Caldera, Valentina ; Nava, Sara ; Ravanini, Maria ; Facchetti, Fabio ; Bruzzone, Maria Grazia ; Finocchiaro, Gaetano. / Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. In: Cancer Research. 2006 ; Vol. 66, No. 21. pp. 10247-10252.
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AU - Pellegatta, Serena

AU - Poliani, Pietro Luigi

AU - Corno, Daniela

AU - Menghi, Francesca

AU - Ghielmetti, Francesco

AU - Suarez-Merino, Bianca

AU - Caldera, Valentina

AU - Nava, Sara

AU - Ravanini, Maria

AU - Facchetti, Fabio

AU - Bruzzone, Maria Grazia

AU - Finocchiaro, Gaetano

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